- Synthesis and antidepressant-like activity of novel aralkyl piperazine derivatives targeting SSRI/5-HT1A/5-HT7
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A series of novel aralkyl piperazine derivatives were synthesized, and evaluated for their serotonin reuptake inhibitory and 5-HT1A/5-HT7 receptors affinities activity. Antidepressant activities in vivo of the compounds were screened using the forced swimming test (FST) and tail suspension test (TST). The results indicated that compounds 21k (RUI, IC50 = 31 nM; 5-HT1A, 5-HT7, ki = 62, 12 nM) and 21n (RUI, IC50 = 25 nM; 5-HT1A, 5-HT7, ki = 28, 3.3 nM) exhibited high affinities for the 5-HT1A/5-HT7 receptors coupled with potent serotonin reuptake inhibition. Specifically, the most promising compound 21n possessed a good oral pharmacokinetic properties and an acceptable hERG profile, and showed potent antidepressant-like effect in the FST and TST models.
- Gu, Zheng-Song,Zhou, Ai-nan,Xiao, Ying,Zhang, Qing-Wei,Li, Jian-Qi
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p. 701 - 715
(2018/01/03)
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- A Photoredox-Induced Stereoselective Dearomative Radical (4+2)-Cyclization/1,4-Addition Cascade for the Synthesis of Highly Functionalized Hexahydro-1H-carbazoles
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A stereoselective synthesis of functionalized hexahydrocarbazoles was developed based on an unprecedented photoredox-induced dearomative radical (4+2)-cyclization/1,4-addition cascade between 3-(2-iodoethyl)indoles and acceptor-substituted alkenes. The title reaction simultaneously generates three C?C bonds and one C?H bond, along with three contiguous stereogenic centers. The hexahydro-1H-carbazole products are highly valuable intermediates for the synthesis of novel antibiotics, as well as unnatural ring homologues of polycyclic indoline alkaloids.
- Alpers, Dirk,Gallhof, Malte,Witt, Julian,Hoffmann, Frank,Brasholz, Malte
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supporting information
p. 1402 - 1406
(2017/01/24)
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- Synthesis of new series of iboga analogues
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Synthesis of new iboga-analogues, replacing the indole ring with a benzofuran moiety has been described. Starting materials are the suitably substituted benzofuran derivatives and have been synthesized by Pd-catalyzed reactions. The conversion of endo-6-m
- Paul, Sibasish,Pattanayak, Sankha,Sinha, Surajit
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supporting information; experimental part
p. 6166 - 6169
(2011/12/01)
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- BENZOFURANYL- AND BENZOTHIENYL- PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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Page/Page column 21-22
(2009/04/24)
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- Halo substituent effects on intramolecular cycloadditions involving furanyl amides
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Intramolecular Diels-Alder reactions involving a series of N-alkenyl-substituted furanyl amides were investigated. Stable functionalized oxanorbornenes were formed in high yield upon heating at 80-110 °C. The cycloaddition reactions include several bromo-substituted furanyl amides, and these systems were found to proceed at a much faster rate and in higher yield than without substitution. This effect was observed by incorporating a halogen in the 3- or 5-position of the furan ring and appears to be general. The origin of increased cycloaddition rates for halo-substituted furans has been investigated with quantum mechanical calculations. The success of these reactions is attributed to increases in reaction exothermicities; this both decreases activation enthalpies and increases barriers to retrocycloadditions. Halogen substitution on furan increases reactant energy and stabilizes the product, which is attributed to the preference of electronegative halogens to be attached to a more highly alkylated and therefore more electropositive framework.
- Padwa, Albert,Crawford, Kenneth R.,Straub, Christopher S.,Pieniazek, Susan N.,Houk
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p. 5432 - 5439
(2007/10/03)
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- Piperidinyl indole and tetrohydropyridinyl indole derivatives and method of their use
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3-Piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed. Methods of using the derivatives and compositions containing the derivatives in the prevention and/or treatment of serotonin disorders, such as depression and anxiety, are also disclosed. Additionally, processes for the preparation of 3-piperidin-4-yl-1H-indole and 3-(1,2,3,6-tetrahydro-pyridin-4-yl)-1H-indole derivatives are disclosed.
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Page/Page column 11
(2010/02/10)
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- BENZOFURANYL-AND BENZOTHIENYL-PIPERAZINYL QUINOLINES AND METHODS OF THEIR USE
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Benzofuranyl-and benzothienyl-piperzinyl quinoline derivatives and compositions containing such compounds are disclosed. Methods of using benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives and compositions containing such composition in the treatment and/or prevention of serotonin-related disorders, such as depression and anxiety, are also disclosed. In addition, processes for the preparation of benzofuranyl- and benzothienyl-piperzinyl quinoline derivatives are disclosed.
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- Intramolecular cyclization reactions of 5-halo- and 5-nitro-substituted furans
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(Matrix presented) Intramolecular cyclization reactions of 5-halo- and 5-nitro-substituted furanylamides were examined. The 2-alkoxy-5-bromofuran derivative 2 produced the rearranged dihydroquinone 6 (36%), a product from the rearrangement of the intermed
- Crawford, Kenneth R.,Bur, Scott K.,Straub, Christopher S.,Padwa, Albert
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p. 3337 - 3340
(2007/10/03)
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- Antidepressant 1-arylalkyl-4-(alkoxy pyridinyl)-and 4-(alkoxypyrimidinyl) piperazine derivatives
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Novel compound of formula I and pharmaceutically acceptable salts thereof are useful CNS agents: STR1 wherein X is CH or N; X' is CH or a direct covalent link; Y is CH, CH2 or N; Y' is N, NH, O or S; R1 is H, Br, Cl, F, C1-4 alkyl, C1-4 alkoxy, C1-4 alkoxycarbonyl, CN, CONH2 or CH3 SO2 NH; n is 2 or 3; R2 is H or C1-4 alkyl; R3 is C1-4 alkoxy; R4 is H, Br, Cl, or F; and Z is CH or N.
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- Antidepressant 1-arylalkyl-4-(alkoxypyridinyl)- or 4-(alkoxypyrimidinyl)piperazine derivatives
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Novel compound of formula I and pharmaceutically acceptable salts thereof are useful CNS agents: wherein X is CH or N; X'is CH or a direct covalent link; Y is CH, CH2or N; Y'is N, NH, O or S; R1is H, Br, Cl, F, C1-4alkyl,
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